bims-reprim 2021-09-26 papers

Issue of 2021–09–26
five papers selected by
Iva Filipovic, Karolinska Institutet

Mucosal Immunol. 2021 Sep 22.

Characterisation of peri-implantation endometrial Treg and identification of an altered phenotype in recurrent pregnancy loss.

Ingrid Granne, Mengni Shen, Helena Rodriguez-Caro, Gurmeher Chadha, Elizabeth O'Donnell, Jan J Brosens, Siobhan Quenby, Tim Child, Jennifer H Southcombe.

Recurrent Pregnancy Loss (RPL) affects 2-4% of couples, and with increasing numbers of pregnancy losses the risk of miscarrying a euploid pregnancy is increased, suggesting RPL is a pathology distinct from sporadic miscarriage that is due largely to lethal embryonic aneuploidy. There are a number of conditions associated with RPL including unspecified "immune" pathologies; one of the strongest candidates for dysregulation remains T regulatory cells as depletion in the very early stages of pregnancy in mice leads to pregnancy loss. Human endometrial Treg and conventional CD4T cells were isolated during the peri-implantation period of the menstrual cycle in normal women. We identified an endometrial Treg transcriptomic signature and validated an enhanced regulatory phenotype compared to peripheral blood Treg. Parous women had an altered endometrial Treg transcriptome compared to nulliparity, indicating acquired immune memory of pregnancy within the Treg population, by comparison endometrial conventional CD4T cells were not altered. We compared primary and secondary RPL to nulliparous or parous controls respectively. Both RPL subgroups displayed differentially expressed Treg gene transcriptomes compared to controls. We found increased cell surface S1PR1 and decreased TIGIT protein expression by Treg in primary RPL, confirming the presence of altered Treg in the peri-implantation RPL endometrium.

DOI: https://doi.org/10.1038/s41385-021-00451-1

Front Cell Infect Microbiol. 2021 ;11 720789

Bacterial and Host Determinants of Group B Streptococcal Vaginal Colonization and Ascending Infection in Pregnancy.

Alyssa Brokaw, Anna Furuta, Matthew Dacanay, Lakshmi Rajagopal, Kristina M Adams Waldorf.

Group B streptococcus (GBS) is a gram-positive bacteria that asymptomatically colonizes the vaginal tract. However, during pregnancy maternal GBS colonization greatly predisposes the mother and baby to a wide range of adverse outcomes, including preterm birth (PTB), stillbirth, and neonatal infection. Although many mechanisms involved in GBS pathogenesis are partially elucidated, there is currently no approved GBS vaccine. The development of a safe and effective vaccine that can be administered during or prior to pregnancy remains a principal objective in the field, because current antibiotic-based therapeutic strategies do not eliminate all cases of invasive GBS infections. Herein, we review our understanding of GBS disease pathogenesis at the maternal-fetal interface with a focus on the bacterial virulence factors and host defenses that modulate the outcome of infection. We follow GBS along its path from an asymptomatic colonizer of the vagina to an invasive pathogen at the maternal-fetal interface, noting factors critical for vaginal colonization, ascending infection, and vertical transmission to the fetus. Finally, at each stage of infection we emphasize important host-pathogen interactions, which, if targeted therapeutically, may help to reduce the global burden of GBS.

Keywords: bacteria; colonization; fetus; group B streptococcus; placenta; pregnancy; preterm birth; vagina

DOI: https://doi.org/10.3389/fcimb.2021.720789

Placenta. 2021 Sep 11. pii: S0143-4004(21)00586-5. [Epub ahead of print]115 37-44

Pandemic stress and SARS-CoV-2 infection are associated with pathological changes at the maternal-fetal interface.

Marie-Eve Brien, Dorothée Bouron-Dal Soglio, Solenn Dal Soglio, Camille Couture, Isabelle Boucoiran, Youssef Nasr, Kate Widdows, Megan C Sharps, Dina El Demellawy, Alexander Ep Heazell, Didier Menzies, Sylvie Girard.

INTRODUCTION: The reported effects of SARS-CoV-2 on pregnancy outcomes are conflicting; studies frequently overlook the placenta, which is critical for the health of the mother and infant(s). This study aimed to determine the effect of pandemic stress ± SARS CoV-2 infection on placental histopathology.
METHODS: Women were recruited in Canada (n = 69); France (n = 21) or in the UK (n = 25), between March and October 2020. Historic controls (N = 20) were also included. Placenta and fetal membrane samples were collected rapidly after delivery and were fixed and stained for histopathological analysis. Maternal demographical data and obstetric outcomes were recorded.
RESULTS: Over 80% of the placentas from SARS-CoV-2+ pregnancies had histopathological abnormalities: predominantly structural (71-86%) or inflammatory (9-22%), depending on geographical location. Excessive fibrin was seen in all sites, whereas deciduitis (Canada), calcifications (UK), agglutinations and chorangiosis (France) predominated in different locations. The frequency of abnormalities was significantly higher than in SARS-CoV-2 negative women (50%, p < 0.05). Demographic and obstetric data were similar in the SARS-CoV-2+ women across all sites - characterised by predominantly Black/Middle Eastern women, and women with elevated body mass index.
DISCUSSION: Overall, the frequency of placental abnormalities is increased in SARS-CoV-2+ women, but the incidence of placental abnormalities is also higher in SARS-CoV-2- women that gave birth during the pandemic, which highlights the importance of appropriate control groups to ascertain the roles of pandemic stress and SARS-CoV-2 infection on the placenta and pregnancy outcomes.

Keywords: Coronavirus disease 2019 (COVID-19); Infection; Pandemic stress; Placenta; Pregnancy; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

DOI: https://doi.org/10.1016/j.placenta.2021.09.007

Cytokine. 2021 Sep 21. pii: S1043-4666(21)00296-9. [Epub ahead of print]148 155707

Elevated inflammatory mediators from the maternal-fetal interface to fetal circulation during labor.

Qian Huang, Xiaolong Jin, Pin Li, Zheng Zheng, Yanmin Jiang, Huishu Liu.

BACKGROUND: Elevated cytokines, like IL-1βand IL-6, are known to contribute to the pathogenesis of labor. However, the change of inflammatory mediators in maternal-fetal interface to fetal circulation is obscure.
STUDY DESIGN AND METHODS: We investigated the changes of inflammatory cytokines, chemokines and macrophage in maternal-fetal interface tissues and fetal circulation of women in labor vs. non-labor. Human myometrium, placenta, decidua, fetal membrane and umbilical blood were obtained from in-labor and non-in-labor women who eventually delivered live, singleton infants at term (>37 weeks gestation) by elective caesarean section. Luminex was used to measure the level of cytokines (TNF-α, IL-1β, IL-6, IL-8) and chemokines (MCP-1, GM-CSF, MIP-1α, MIP-1β) in each sample (tissue and umbilical blood). Macrophage infiltration was demonstrated by immunohistochemistry.
RESULTS: During labor, the level of cytokines TNF-α, IL-1β, IL-6 and IL-8 and chemokine MCP-1 and MIP-1β in myometrium is significantly higher (p < 0.05), than those obtained from non-laboring patients. This increase coincides with the influx of macrophage into the myometrium. In addition, IL-1β and IL-8 (p < 0.05) are also up regulated in fetal membrane during labor compared to non-labor. The cytokines do not change significantly in placenta and decidua tissue. In fetal circulation, IL-6 (p < 0.05) is up regulated in umbilical vein blood in labor group. IL-8 (p = 0.08) in umbilical vein also show an increasing trend during labor.
CONCLUSIONS: There are markedly elevated inflammatory mediators in maternal-fetal interface during labor. The increased maternal inflammatory factors released into the fetal circulation through placenta circulation at the time of labor. This increase coincides with the influx of macrophage into the pregnancy tissue, suggesting that the inflammatory response might play an important role in the onset of labor.

Keywords: Fetal circulation; Inflammation; Labor; Maternal-fetal interface; Myometrium

DOI: https://doi.org/10.1016/j.cyto.2021.155707

Cell Prolif. 2021 Sep 21. e13125

Single-cell transcriptome analysis reveals defective decidua stromal niche attributes to recurrent spontaneous abortion.

Lili Du, Wenbo Deng, Shanshan Zeng, Pei Xu, Lijun Huang, Yingyu Liang, Yang Wang, Hui Xu, Jingman Tang, Shilei Bi, Lizi Zhang, Yulian Li, Luwen Ren, Lin Lin, Weinan Deng, Mingxing Liu, Jingsi Chen, Haibin Wang, Dunjin Chen.

OBJECTIVES: Successful pregnancy involves the homeostasis between maternal decidua and fetoplacental units, whose disruption contributes to compromised pregnancy outcomes, including recurrent spontaneous abortion (RSA). The role of cell heterogeneity of maternal decidua in RSA is yet to be illustrated.
MATERIALS AND METHODS: A total of 66,078 single cells from decidua samples isolated from patients with RSA and healthy controls were analysed by unbiased single-cell RNA sequencing (scRNA-seq).
RESULTS: Our scRNA-seq results revealed that stromal cells are the most abundant cell type in decidua during early pregnancy. RSA samples are accompanied by aberrant decidualization and obviously obstructed communication between stromal cells and other cell types, such as abnormal activation of macrophages and NK cells. In addition, the over-activated TNF superfamily member 12 (TNFSF12, TWEAK) and FASLG in RSA are closely related to stromal cell demise and pregnancy failure.
CONCLUSIONS: Our research reveals that the cell composition and communications in normal and RSA decidua at early pregnancy and provides insightful information for the pathology of RSA and will pave the way for pregnancy loss prevention.

DOI: https://doi.org/10.1111/cpr.13125